title: A multicenter phase I-II study of docetaxel plus epirubicin plus bevacizumab as first-line treatment in women with HER2-negative metastatic breast cancer.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC).
  
  
  METHODS
  Women with previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m2) and D (75 mg/m2) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using the CellSearch system at different time points during therapy.
  
  
  RESULTS
  Eighty-three women were enrolled with median age 62 years, performance status 0-1 in 93%, triple negative disease in 12% and liver metastases in 47%. In an intention to treat analysis, complete response was achieved in 13 (15.7%) and partial response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09-76.44%). The median time to progression was 20.1 months and the 1-year overall survival rate 82.3%. Grade 3-4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n = 1; sudden death n = 1). Moreover, one patient developed pulmonary embolism and another one myocardial infarction while on treatment. Although DEB administration significantly reduced the proportion of patients presenting CTCs, the detection of ≥5 or ≥1 CTCs before treatment initiation was significantly associated with worse progression-free survival (p = 0.001 and p = 0.004) and overall survival (p = 0.001 and p = 0.027), respectively.
  
  
  CONCLUSIONS
  The DEB regimen is a very active but also potentially toxic combination in MBC. Detection of CTCs before treatment is associated with worse outcome.
  
  
  BACKGROUND
  NCT00705315.
authors.affiliation: Hellenic Oncology Research Group, 55 Lombardou Street, 11474 Athens, Greece(1).
authors.forename: K
authors.initials: K
authors.lastname: Tryfonidis
authors.forename: I
authors.initials: I
authors.lastname: Boukovinas
authors.forename: N
authors.initials: N
authors.lastname: Xenidis
authors.forename: C
authors.initials: C
authors.lastname: Christophyllakis
authors.forename: P
authors.initials: P
authors.lastname: Papakotoulas
authors.forename: E
authors.initials: E
authors.lastname: Politaki
authors.forename: N
authors.initials: N
authors.lastname: Malamos
authors.forename: A
authors.initials: A
authors.lastname: Polyzos
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D009503:Neutropenia / Q000139:chemically induced; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077143:Docetaxel; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human
keywords: Bevacizumab; CTC; Docetaxel; Epirubicin; MBC